Cholera toxin (CT) is known to inhibit the proliferation of murine and human T lymphocytes. In this study we have analysed the mechanisms underlying the inhibitory effect of CT on subpopulations of human CD4+and CD8+T lymphocytes. We show that CT dramatically prevents the activation of resting T lymphocytes, whereas it has a minor effect on cells that have been previously activated. Analysis of DNA content of the CT-treated T cells showed an arrest in the G0/G1phase and this correlated with high expression of the cyclin-dependent kinase inhibitor p27kip. Moreover, we show that CT up-regulates the expression of the inhibitory molecule CTLA-4 in naïve, effector and memory resting CD4+T cells and in resting CD8+T lymphocytes. The regulation of CTLA-4 expression by CT is at the transcriptional level. Indeed, in cells treated with CT we observed an increase of two mRNA variants coding for the membrane and the soluble CTLA-4 molecules. In parallel with the up-regulation of the inhibitory CTLA-4, CT down-modulates the costimulatory molecule CD28 on CD4+and CD8+resting T cells. The increased expression of CTLA-4 played a role in controlling T cell activation and function as blocking anti-CTLA-4 F(ab′)2mAbs partially inhibited anti-CD3 mAbs induced proliferation. These findings show that the inhibition of T cell proliferation by CT affects early stages of the T cell activation and involves the modulation of costimulatory molecules CTLA-4 and CD28 on resting T cells. © 2007 Elsevier B.V. All rights reserved.
All Science Journal Classification (ASJC) codes
- Immunology and Allergy
Vendetti, S., Riccomi, A., Sacchi, A., Sciaraffia, E., Gatta, L., Pioli, C., & De Magistris, M. T. (2008). Inhibition of T cell proliferation by cholera toxin involves the modulation of costimulatory molecules CTLA-4 and CD28. Immunology Letters, 115(1), 59 - 69. https://doi.org/10.1016/j.imlet.2007.10.003